Reye’s Syndrome: A complete guide

Like most serious medical conditions, early intervention is a matter of life or death. However, rare illnesses often go undetected simply because not enough people recognize the signs and symptoms. It is a rare, potentially fatal disease of the liver and brain. Awareness is important to save the lives of the children and adults who develop Reye’s Syndrome after a viral infection.   

What is Reye’s Syndrome?

Reye’s syndrome is classified as a metabolic encephalopathy. The rare disorder results in fatty deposits on the liver and other organs in the body, as well as an increase in pressure (swelling) in the brain. According to the National Reye’s Syndrome Foundation, it is a two-phase illness. It is known to occur in the recovery stage of a viral illness, like a cold or the flu, treated with the use of aspirin and salicylate-containing medications.

Children ages 4 through 12 are especially susceptible to developing the condition, but teenagers, adults, and infants may be affected. Early treatment is key to prevent death or long-term brain deficits.

Physical Symptoms of Reye’s Syndrome

Symptoms of Reye’s syndrome typically begin subsequent to an upper respiratory infection from the flu or a cold, chickenpox, or a stomach virus. The time of onset varies from 1 day to 2 weeks after a viral illness and symptoms continue to progress without medical treatment. 

• Vomiting—Sudden, uncontrollable vomiting is generally the first symptom.
• Lethargy—Shortly after the onset of vomiting, an overwhelming need for sleep takes over. Alterations in consciousness can follow.
• Dilated pupils (mydriasis)—The opening of the iris in the eye becomes larger than normal.  
• Rapid pulse (tachycardia)—Heartrate is elevated and beats more times a minute.  
• Enlargement of liver (hepatomegaly)—Since Reye’s syndrome interferes with liver function, swelling of the liver called hepatomegaly accompanies increased hepatic enzymes.
• Weakness—Patients with the condition experience weakness in their arms and legs that can progress to paralysis.
• Ataxia—Losing control of the muscle movements leads to rigidity and unwanted muscle postures.  
• Loss of reflexes—Reflexes test the functioning of various muscles controlled by the central nervous system. Deep tendon reflexes, pupillary reflexes, and oculocephalic reflexes decline.
• Seizures—Abnormal electrical activity causes seizures as Reye’s syndrome further compromises the brain and nervous system.  
• Unresponsiveness (coma)—If left untreated, symptoms may progress to a coma.
• High ammonia levels (hyperammonemia)—Ammonia levels in the blood increase and are toxic to the brain.

Psychological Symptoms of Reye’s Syndrome

In addition to the miscellaneous physical symptoms described above, Reye’s syndrome also has a psychological influence because the condition primarily impacts the brain. Sudden behavioral changes, such as irritability and aggressiveness, are common. Individuals with this syndrome frequently report confusion with memory impairment—almost like a lack of awareness of one’s surroundings. Hallucinations and delusions result in severe cases.

Infants with Reye’s Syndrome

Infants with Reye’s syndrome differ in presentation in comparison to older children or adults. While they display the other symptoms too, the condition starts with rapid, fast-paced breathing and diarrhea. The beginning sign of vomiting is not as prevalent.

Causes of Reye’s Syndrome

The exact cause of it currently remains unknown. However, experts do have a biological explanation. The body’s mitochondria become damaged. Mitochondria are the powerhouses of a cell. They provide energy to complete daily tasks like liver function. If these mitochondria are not functioning optimally, neither are the body’s organs. Toxic substances begin to accumulate in the blood. The liver is overwhelmed, the brain swells, and the central nervous system suffers. Experts have also established that symptoms of it proceed with a viral infection, which can be a mitochondrial stressor.

This Syndrome and Aspirin

There is a notable association between Reye’s syndrome and viral illnesses such as a cold, the flu, or a respiratory virus AND taking salicylate-containing medications during the course of the virus. Salicylate-containing medications like aspirin disrupt fatty acid metabolism in the liver. As fatty acid metabolism is hindered, the liver and mitochondria are injured. A viral illness contributes to the stress on the mitochondria in the liver. The liver is then unable to do its job by filtering toxins out of the body and this buildup of toxins causes symptoms of Reye’s syndrome. 90% of cases are caused by aspirin use. Limited the use of aspirin in children has substantially decreased the frequency within that population of patients.

This Syndrome and Metabolic Disorders

Specific types of metabolic disorders, such as fatty acid oxidation disorders, make someone prone to the symptoms. Fatty acid oxidization disorders are mitochondrial disorders characterized by alterations in lipid metabolism. The inability to breakdown fats causes a metabolic crisis. Elevated ammonia levels in the blood and hypoglycemia cause similar effects on the nervous system. When it is suspected, professionals recommend to also test for inborn errors of metabolism like fatty acid oxidation disorder.

Diagnosing Reye’s Syndrome

Diagnosing Reye’s syndrome relies on a thorough history taken by a doctor. Along with the clinical signs and symptoms, blood and urine tests help confirm the diagnosis. Basic show for evidence of liver dysfunction. They also screen for underlying metabolic conditions associated with it. If the non-invasive tests, such as neuroimaging, do not provide enough information, the physician might resort to more invasive procedures.

• Lumbar puncture—A lumbar puncture or spinal tap involves removing fluids from the spine using a hollow needle to test whether there is inflammation of the brain or an infection in the membrane surrounding the brain and spinal cord.  
• Skin biopsy—A skin biopsy is a diagnostic tool to confirm a fatty acid oxidation disorder—a possible underlying cause for Reye’s syndrome.
• Liver biopsy—A sample of liver tissue is retrieved with a needle inserted into the abdomen. Lab analysis will determine the extent of liver damage caused by Reye’s syndrome or rule out separate conditions responsible for liver symptoms.
• Electroencephalogram (EEG)—Seizures are a common manifestation. An EEG measures the abnormal brain waves.
• Computerized tomography (CT) Scan—Computerized tomography (CT) combines x-ray images of various angles. This test is ordered to rule out causes of behavioral changes.  
• Magnetic resonance imaging (MRI)—Magnetic resonance imaging (MRI) depicts the internal structure of the body through magnetic waves. It is another way to rule out causes for behavioral changes that do not require radiation.

Conditions Commonly Mistaken With This Syndrome

Considering the rarity of Reye’s syndrome, even medical professionals tend to overlook its signs and symptoms. Organ involvement is extensive, so it is often mistaken for conditions producing similar symptoms.

• Viral Encephalitis—Inflammation of the brain from a virus mimics vomiting, headache, confusion, and fever displayed in the first stages of Reye’s syndrome.
• Meningitis—Meningitis is inflammation of the membranes surrounding the brain and spinal cord.
• Drug overdose or poisoning—Certain substances unsafe for consumption create the same symptoms as Reye’s syndrome.  
• Diabetes—Prolonged elevated blood sugar levels due to the body’s inability to use the hormone insulin leads to confusion, vomiting, and eventually loss of consciousness.  
• Sudden Infant Death Syndrome—Sudden infant death syndrome is when a previously healthy infant dies suddenly during sleep. It can result in death within hours, sometimes before parents realize there is a medical emergency.
• Head trauma—An injury to the skull or brain provoke a variety of neurological symptoms.
• Kidney failure—The main symptoms of kidney failure are vomiting, confusion, swelling, and fatigue. Kidney failure from other causes aside from Reye’s syndrome are occasionally suspected.
• Psychiatric illness—The hallucinations and confusion appear as psychiatric illness.

Treatment for Reye’s Syndrome

It is a medical emergency. Its treatment is multifaceted. Physicians determine the intervention based on the patient’s severity. However, the focus of treatment is always to correct metabolic abnormalities that may arise, assist difficulty breathing, and monitor increased intracranial pressure—the pressure between the skull and the brain. Treatment consists of any of the following:

• Monitor vital functions—Vital functions include heart rate, blood pressure, respiration, circulation, and body temperature.
• Fluids and electrolytes—It interferes with how the body balances its fluid levels and electrolytes to maintain energy for regular functions. The metabolic crisis induces a plethora of abnormalities. Patients are given. Extra hydration, electrolytes, and dextrose through an IV.
• Anticonvulsants—Uncontrolled seizures are treated with anticonvulsants.
• Ventilator—A ventilator pushes air into the lungs for patients unable to breathe and maintain oxygen levels on their own.  
• Antibiotics—Although it is not an infection, antibiotics can decrease elevated ammonia levels that build up in the blood.
• Steroids—Steroids are medications used to decrease inflammation. In the case of this syndrome, steroids are given to lessen brain swelling.
• Diuretics—Excess fluid develops around the brain and diuretics are given to decrease the water surrounding the brain.
• Mannitol—Elevated intracranial pressure has also been known to respond to mannitol.
• Vitamin K therapy—The buildup of ammonia in the blood can result in bleeding disorders. Vitamin K therapy is the optimal treatment for that complication.

Brain Damage After Reye’s Syndrome

While the majority of patients treated early do not sustain lasting damage from Reye’s syndrome, recovery is not as swift for those diagnosed in its later stages. Unfortunately, the brain swelling can produce lasting repercussions on the nervous system. The effects range from no damage to extensive brain injury. Possible long term complications are poor attention span, memory loss, vision or hearing troubles, difficulty swallowing, speech problems, and a decline in motor skills. The exact symptoms depend on the part of the brain most compromised from the individual’s case of Reye’s syndrome. The efforts of doctors, psychologists, physical or occupational therapists, and loved ones help the patient surmount these life-altering challenges.

References

Demczko, M. (2018). Fatty Acid Oxidation Disorders. Retrieved from https://www.merckmanuals.com/home/children-s-health-issues/hereditary-metabolic-disorders/fatty-acid-oxidation-disorders

Gosalakkal, J.A. & Kamoji, V. (2008). Reye Syndrome and Reye-Like Syndrome. Pediatric Neurology. Volume 39, Issue 3, Pages 198–200.

National Reye’s Syndrome Foundation. (2013). What is Reye’s Syndrome. Retrieved from https://www.reyessyndrome.org/index.html

Cheyanne Perry

Cheyanne is currently studying psychology at North Greenville University. As an avid patient advocate living with Ehlers Danlos Syndrome, she is interested in the biological processes that connect physical illness and mental health. In her spare time, she enjoys immersing herself in a good book, creating for her Etsy shop, or writing for her own blog.